Membrane Channels Research Articles

The Involvement of Calcium Channels in the Endoplasmic Reticulum Membrane in Nonalcoholic Fatty Liver Disease Pathogenesis.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent and complex condition that affects millions of people globally. It occurs when fat, primarily triglycerides, accumulates in liver cells, leading to inflammation and damage. Calcium, an essential mineral, is involved in various physiological processes, including the regeneration process following liver injury. The endoplasmic reticulum (ER), a complex organelle involved in protein synthesis and lipid metabolism, regulates intracellular calcium levels. Dysregulation of this process can lead to calcium overload, oxidative stress, and cellular damage, all of which are hallmarks of NAFLD. Inositol 1,4,5-trisphosphate receptor (IP3R), a type of calcium ion channel, is found throughout the body, including the liver. IP3R is classified into three subtypes: IP3R1, IP3R2, and IP3R3, and it plays a critical role in regulating intracellular calcium levels. However, excessive calcium accumulation in the mitochondria due to an overload of calcium ions or increased IP3R activity can lead to NAFLD. Therefore, targeting calcium channels in the ER membrane may represent a promising therapeutic strategy for preventing and treating this increasingly prevalent metabolic disorder.It may help prevent mitochondrial calcium accumulation and reduce the risk of hepatic damage. This review article aimed to review the relationship between IP3R modulation and the pathogenicity of NAFLD, providing valuable insights to help researchers develop more effective treatments for the condition.

Constructing ultra-permeable pillar[5]arene-based membrane with intramolecular water channels and precise molecular fractionation

Designing membranes with synthetic water channels has become an emerging topic to overcome the ubiquitous selectivity/permeability trade-off effect. In this study novel ultra-permeable thin film composite membranes with precise molecular fractionation were successfully fabricated. Per-hydroxylated pillar [5]arene (P [5]A), a macrocycle with a highly regular, cylindrical, angstrom-scale intramolecular cavity was applied as the aqueous monomer in interfacial polymerization (IP) to construct water channels in a thin film composite membrane. The competing effects of esterification and alkali-induced hydrolysis during IP were validated by investigating the effect of fabrication conditions. With almost complete rejection of model dyes >99.0% (e.g., Congo Red & Direct Red 23) and low retention of salts (e.g., 4.5% for NaCl & 18.9% for Na2SO4), the optimal membrane exhibited an ultra-high water permeance up to 267.1 L m−2 h−1 bar−1, which is 3–10 times higher than most literature-reported membranes for similar applications. Also, the precision of dye/salt fractionation of the membrane was not affected by the increased feed salinity, with overall stable performance in 72 h continuous operation. A high flux recovery of >94.5% proved that the membrane had low fouling propensity. Overall, the new route explored in this study provided inspiration for designing ultra-permeable membranes with precise molecular separation for environmental applications.

Numerical study of Tesla valve flow field on proton exchange membrane fuel cell performance

Effective flow channels in proton exchange membrane fuel cells (PEMFCs) can provide sufficient reactant and a more uniform reactant distribution, which allows the fuel cells to operate with high performances. The Tesla valve structure is thought to be a feasible structure for channel design due to its one-directional flow characteristics, yielding different performances with different flow directions. Numerical studies were conducted in this work to investigate the impacts of the channel structure, flow direction, and excess air coefficient on the fuel cell performance. Three types of flow channels (straight, symmetric Tesla valve, and asymmetric Tesla valve) and two flow directions (forward and reverse) were studied. The results showed that the maximum power density of the reversed asymmetric Tesla valve increased by 10.08 % compared to that of the conventional straight channel. Detailed research revealed that the Tesla valve resulted in a more intense flow than the conventional straight channel. The symmetric Tesla valve resulted in a greater pressure drop than the asymmetric valve. The Tesla valves with reverse flow could significantly limit the formation of an oxygen dead zone. Hence, enhanced Z-direction mass transfer and the lowest standard deviations of the oxygen and water distributions were observed. The effects of the excess air coefficient on the net power density were also studied. Increasing the excess air mass to the cathode facilitated the enhancement of the electrode voltage but required more parasitic power due to the growth in the pressure drop along the flow channel.

Impact of spacer on membrane gas separation performance

Mixing in gas separation membranes has received much less attention than in membrane liquid separation because gas molecules have much smaller viscosity, allowing them to diffuse easily through membranes without requiring significant flow mixing. However, due to advancements in membrane fabrication technologies aimed at improving material properties, concentration polarization (CP) might become an issue in gas separation due to enhanced membrane efficiency and permeability. Consequently, a 2D CFD analysis is conducted to evaluate the impact of spacer-induced mixing on membrane gas concentration polarization for typical CO2/CH4 gas separation. Results show that spacers generally enhance flux performance while reducing CP in the membrane channel when compared to the case without spacers. Furthermore, the effectiveness of spacer-flux-to-pressure-loss-ratio (SPFP) reaches a peak for a Reynolds number in the range of 5 <Reh< 200 because of the trade-off between flux and pressure drop. This mixing-induced flux enhancement is most effective under high CP conditions (less mixing) within the membrane channel. Similarly, flux enhancement due to spacers can be observed as membrane selectivity, pressure ratio and feed gas concentration increase due to enhanced CP.

IK Channel-Independent Effects of Clotrimazole and Senicapoc on Cancer Cells Viability and Migration.

Many studies highlighted the importance of the IK channel for the proliferation and the migration of different types of cancer cells, showing how IK blockers could slow down cancer growth. Based on these data, we wanted to characterize the effects of IK blockers on melanoma metastatic cells and to understand if such effects were exclusively IK-dependent. For this purpose, we employed two different blockers, namely clotrimazole and senicapoc, and two cell lines: metastatic melanoma WM266-4 and pancreatic cancer Panc-1, which is reported to have little or no IK expression. Clotrimazole and senicapoc induced a decrease in viability and the migration of both WM266-4 and Panc-1 cells irrespective of IK expression levels. Patch-clamp experiments on WM266-4 cells revealed Ca2+-dependent, IK-like, clotrimazole- and senicapoc-sensitive currents, which could not be detected in Panc-1 cells. Neither clotrimazole nor senicapoc altered the intracellular Ca2+ concentration. These results suggest that the effects of IK blockers on cancer cells are not strictly dependent on a robust presence of the channel in the plasma membrane, but they might be due to off-target effects on other cellular targets or to the blockade of IK channels localized in intracellular organelles.

Dimerization mechanism of an inverted-topology ion channel in membranes.

Many ion channels are multisubunit complexes where oligomerization is an obligatory requirement for function as the binding axis forms the charged permeation pathway. However, the mechanisms of in-membrane assembly of thermodynamically stable channels are largely unknown. Here, we demonstrate a key advance by reporting the dimerization equilibrium reaction of an inverted-topology, homodimeric fluoride channel Fluc in lipid bilayers. While the wild-type channel is a long-lived dimer, we leverage a known mutation, N43S, that weakens Na+ binding in a buried site at the interface, thereby unlocking the complex for reversible association in lipid bilayers. Single-channel recordings show that Na+ binding is required for fluoride conduction while single-molecule microscopy experiments demonstrate that N43S Fluc exists in a dynamic monomer-dimer equilibrium in the membrane, even following removal of Na+. Quantifying the thermodynamic stability while titrating Na+ indicates that dimerization occurs first, providing a membrane-embedded binding site where Na+ binding weakly stabilizes the complex. To understand how these subunits form stable assemblies while presenting charged surfaces to the membrane, we carried out molecular dynamics simulations, which show the formation of a thinned membrane defect around the exposed dimerization interface. In simulations where subunits are permitted to encounter each other while preventing protein contacts, we observe spontaneous and selective association at the native interface, where stability is achieved by mitigation of the membrane defect. These results suggest a model wherein membrane-associated forces drive channel assembly in the native orientation while subsequent factors, such as Na+ binding, result in channel activation.

Highly enantioseparation in membrane-supported one-dimensional metal–organic framework hollow nanotube array prepared via mussel-inspired chemistry

High-enantioselective chiral metal–organic framework (CMOF) nanochannel membranes are of critical importance for chiral enantiomeric separations by taking advantage of their inherent high porosity and intrinsic chirality. However, traditional chiral membranes are still constrained by the permeability-selectivity trade-off, making it challenging to improve both simultaneously. This study described the structure of a new class of membrane-supported one-dimensional MOF hollow nanotube for transport and separation of chiral 1-phenylethanol (PE), utilizing a biomimetic polydopamine (PDA)-mediated counter-diffusion synthesis strategy. The inner cylindrical pore channel surface of polycarbonate track-etched membranes (PCTM) was modified by PDA chemistry to control the nucleation and interfacial growth of CMOF crystals, leading to the development of integrated chromatographic micro-column array membranes PCTM@PDA@Cu2C2D and PCTM@PDA@Cu2C2B with one-dimensional (1D) CMOF hollow nanochannels. Compared to PCTM@PDA@Cu2C2B, it was highlighted that the chiral membrane PCTM@PDA@Cu2C2D possessed the higher loading of Cu2C2D functional layer and more suitable steric chiral microenvironment, thus exhibited more outstanding permeability and selectivity for S-PE enantiomer with an enantiomeric excess value up to 90 % under an optimal guest concentration of 250 ppm at 30 °C for 1 h. The chiral membrane with 1D MOF hollow nanotubes, created by applying a gentle and simple method to introduce CMOF into the surface and pore channels of the substrate membrane, was expected to be utilized for the large-scale production of chiral separation membranes for industrial applications.

Bacteria manipulate host cells with channel-forming effectors

Bacterial pathogens deliver effectors into host cells mostly to manipulate signaling and metabolic molecules, thereby subverting host immunity. A recent study by Nomura et al. demonstrates that certain effectors create membrane channels in host cells, enabling bacteria to access water and solutes for multiplication.

The Effect of Calcium Ions on hIAPP Channel Activity: Possible Implications in T2DM.

The calcium ion (Ca2+) has been linked to type 2 diabetes mellitus (T2DM), although the role of Ca2+ in this disorder is the subject of intense investigation. Serum Ca2+ dyshomeostasis is associated with the development of insulin resistance, reduced insulin sensitivity, and impaired glucose tolerance. However, the molecular mechanisms involving Ca2+ ions in pancreatic β-cell loss and subsequently in T2DM remain poorly understood. Implicated in the decline in β-cell functions are aggregates of human islet amyloid polypeptide (hIAPP), a small peptide secreted by β-cells that shows a strong tendency to self-aggregate into β-sheet-rich aggregates that evolve toward the formation of amyloid deposits and mature fibrils. The soluble oligomers of hIAPP can permeabilize the cell membrane by interacting with bilayer lipids. Our study aimed to evaluate the effect of Ca2+ on the ability of the peptide to incorporate and form ion channels in zwitterionic planar lipid membranes (PLMs) composed of palmitoyl-oleoyl-phosphatidylcholine (POPC) and on the aggregation process of hIAPP molecules in solution. Our results may help to clarify the link between Ca2+ ions, hIAPP peptide, and consequently the pathophysiology of T2DM.

Implications of deltamethrin on hematology, cardiac pathology, and gene expression in Nile tilapia (Oreochromis niloticus) and its possible amelioration with Shatavari (Asparagus racemosus).

Deltamethrin (DM) is one of the extensively used pyrethroids for controlling ectoparasites. Unfortunately, DM is highly toxic to fish as it primarily targets the sodium channels of the plasma membrane thereby affecting their cardiac and nervous systems. The present study investigated the protective efficacy of Shatavari (Asparagus racemosus) against DM-induced cardiotoxicity in Nile tilapia (Oreochromis niloticus). The fish were segregated into nine groups having 36 fish/group maintained in triplicates exposed to DM (1µg/L) and fed with a diet containing three different concentrations (10g, 20g, and 30g/kg feed) of aqueous extract of A. racemosus (ARE) for 21 days. DM caused significant alterations in the blood and serum parameters, and expression of cardiac and apoptotic genes compared to the control group. The ARE cotreatment significantly reduced the increase in serum transaminases, creatine kinase, and lactate dehydrogenase levels induced by DM. ARE facilitated the regain of electrolyte (sodium, potassium, chloride) homeostasis and antioxidants such as catalase, superoxide dismutase, glutathione peroxidase, and glutathione in DM-exposed fish. The cardiac histology exhibited loose separation of the cardiomyocytes and myofibrillar loss in the DM group which was ameliorated in the DM-ARE cotreatment group. Significant modulations were observed in the expression of cardiac-specific genes (gata4, myh6, tnT, cox1) and apoptosis signaling genes and proteins (HSP70, bax, bcl-2, caspase3), in the cotreatment group compared to the DM-exposed group. The current study suggests that ARE possesses potential cardioprotective properties that are effective in mitigating the toxic effects induced by DM via ameliorating oxidative stress, electrolyte imbalance, and apoptosis in tilapia.

Composite proton exchange membrane for fuel cells based on chitosan modified by acid-base amphoteric nanoparticles

Currently, achieving a simultaneous improvement in proton conductivity and mechanical properties is a key challenge in using chitosan (CS) as a proton exchange membrane (PEM) substrate in direct methanol fuel cells (DMFCs). Herein, a novel nanofiller–zwitterionic molecule, (3-(3-aminopropyl) dimethylammonio) propane-1-sulfonate, ADPS)-modified polydopamine (PDA) (PDA-ADPS) was synthesized by the Michael addition reaction and was incorporated into a CS matrix to prepare CS/PDA-ADPS composite membranes. PDA-ADPS, which contains an acid–based ion pair can create new proton conduction channels in the composite membrane, improving proton conductivity. The proton conductivity of the CS/PDA-ADPS composite membrane was as high as 38.4 mS cm−1 at 80 °C. Moreover, due to the excellent compatibility and dispersibility of PDA-ADPS in the CS matrix, the obtained CS/PDA-ADPS composite membranes exhibited favorable mechanical properties. Such outstanding proton conductivity and mechanical properties guarantee good performance of the composite membranes in fuel cells. The peak power density of the CS/PDA-ADPS composite membranes was 30.2 mW cm−2 at 70 °C. This work provides a new strategy for fabricating high-performance CS based PEMs for DMFCs.

Identification and Characterization of Tunneling Nanotubes for Intercellular Trafficking.

Tunneling nanotubes (TNTs) are thin membranous channels providing a direct cytoplasmic connection between remote cells. They are commonly observed in different cell cultures and increasing evidence supports their role in intercellular communication, and pathogen and amyloid protein transfer. However, the study of TNTs presents several pitfalls (e.g., difficulty in preserving such delicate structures, possible confusion with other protrusions, structural and functional heterogeneity, etc.) and therefore requires thoroughly designed approaches. The methods described in this protocol represent a guideline for the characterization of TNTs (or TNT-like structures) in cell culture. Specifically, optimized protocols to (1) identify TNTs and the cytoskeletal elements present inside them; (2) evaluate TNT frequency in cell culture; (3) unambiguously distinguish them from other cellular connections or protrusions; (4) monitor their formation in living cells; (5) characterize TNTs by a micropatterning approach; and (6) investigate TNT ultrastructure by cryo-EM are provided. Finally, this article describes how to assess TNT-mediated cell-to-cell transfer of cellular components, which is a fundamental criterion for identifying functional TNTs. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Identification of tunneling nanotubes Alternate Protocol 1: Identifying the cytoskeletal elements present in tunneling nanotubes Alternate Protocol 2: Distinguishing tunneling nanotubes from intercellular bridges formed during cell division Basic Protocol 2: Deciphering tunneling nanotube formation and lifetime by live fluorescent microscopy Alternate Protocol 3: Deciphering tunneling nanotube formation using a live-compatible dye Basic Protocol 3: Assessing tunneling nanotubes functionality in intercellular transfer Alternate Protocol 4: Flow cytometry approach to quantify the rate of vesicle or mitochondria transfer Support Protocol: Controls to support TNT-mediated transfer Basic Protocol 4: Studies of tunneling nanotubes by cell micropatterning Basic Protocol 5: Characterization of the ultrastructure of tunneling nanotubes by cryo-EM.

Synchronously improved permeability, selectivity and fouling resistance of Fe-N-C functionalized ceramic catalytic membrane for effective water treatment: The critical role of Fe

Constructing catalytic membrane simultaneously displaying high permeability, selectivity and antifouling performance in water treatment remains challenging. Herein, the surface and pore channels of the ceramic membrane were co-functionalized with nitrogen doped carbon supported Fe catalyst (CN-F), and the Fe content was varied to investigate its effect on performance of CN-F coupled with peroxymonosulfate (PMS) activation (CN-F/PMS) for water treatment. Results confirmed the introduced Fe (in Fe-N coordination form) greatly enhanced the permeability, selectivity and fouling resistance of CN-F. Optimal CN-F3/PMS achieved 96.5% removal and 52.1% mineralization of sulfamethoxazole in short retention duration (2.7 min), whose performance was 5.4 and 6.7 times higher than that of nitrogen doped carbon functionalized ceramic catalytic membrane (CN/PMS) and CN-F3 filtration alone, respectively. CN-F3/PMS also efficiently inhibited fouling on both surface and pores with 2.8 and 2.4 times lower flux loss than that of CN/PMS and CN-F3 filtration alone, respectively. Moreover, CN-F3/PMS displayed superior performance in long-term treatment of real coking wastewater. The outstanding performance of CN-F was mainly attributed to the dual role of supported Fe, which served as hydrophilic site for enhanced water permeation and major active site for PMS adsorption and reduction into reactive species (mainly high-valent Fe(IV)=O species) towards pollutant elimination.

Effect of permeable spacer structure on energy loss and mass transfer in reverse osmosis membrane modules

This study used numerical simulation to investigate the effects of a novel permeable cylindrical-flow distributor on energy loss and mass transfer in reverse osmosis (RO) membrane modules. The analysis focused on variables, such as Reynolds number, inlet concentration and flow incidence angle, influencing the improvement of water production efficiency in RO membranes and the reduction of concentration polarisation on the membrane surface. The membrane surface shear stress, vorticity, permeate flux and concentration polarisation factor were used to describe these effects. To better explain the performance of the permeable flow distributor, the viscous resistance coefficient (Du) in the porous media model was used to measure the permeability of the flow distributor. Furthermore, a produced water energy consumption factor (JCP) was defined to represent the energy required for unit water production. The results indicate that the permeable flow distributor significantly reduces pressure loss in the membrane channels, avoiding the high energy consumption associated with traditional flow distributors in RO processes. The Du exhibits an optimal value in the range of 1e8 to 1e10, which maximises the JCP, leading to a 32.9 % improvement compared to traditional impermeable flow distributors. This achievement enables energy-efficient and effective desalination of seawater.

Reversal of Supraventricular Tachycardia with Aberration afte Initiation of Pseudoanalgesia with Propofol: Case Report

Supraventricular tachycardia (SVT) is a heterogeneous group of arrhythmias used to describe tachycardias involving cardiac tissue at or above the level of the bundle of His. They usually appear in subjects without structural heart disease. However, they can sometimes cause palpitations, dyspnea, sweating, angina, or vague chest discomfort, particularly in patients with underlying heart disease. We present the case of a patient with SVT reverted during pseudonalgesia with propofol. This is a 48-year-old male patient who came for presenting a sensation of intense palpitations, an electrocardiogram was taken where the presence of wide QRS tachycardia was observed. It was decided to administer procedural sedation for synchronized electrical cardioversion, however, he presented cardioversion upon administration of propofol 50 mg (Fig 1B) after 5 minutes, improving the symptoms. Studies of propofol have described its influence on the cardiac conduction system and the ability to modify the phases of the action potential by acting on the ion channels of the myocyte membrane. Therefore, it would be interesting to see case series from large centers and electrophysiology studies that show the possible antiarrhythmic role of drugs such as propofol not described in the literature.

Reconstitution of a minimal ESX-5 type VII secretion system suggests a role for PPE proteins in the outer membrane transport of proteins.

Mycobacteria utilize type VII secretion systems (T7SSs) to secrete proteins across their highly hydrophobic and diderm cell envelope. Pathogenic mycobacteria have up to five different T7SSs, called ESX-1 to ESX-5, which are crucial for growth and virulence. Here, we use a functionally reconstituted ESX-5 system in the avirulent species Mycobacterium smegmatis that lacks ESX-5, to define the role of each esx-5 gene in system functionality. By creating an array of gene deletions and assessing protein levels of components and membrane complex assembly, we observed that only the five components of the inner membrane complex are required for its assembly. However, in addition to these five core components, active secretion also depends on both the Esx and PE/PPE substrates. Tagging the PPE substrates followed by subcellular fractionation, surface labeling and membrane extraction showed that these proteins localize to the mycobacterial outer membrane. This indicates that they could play a role in secretion across this enigmatic outer barrier. These results provide the first full overview of the role of each esx-5 gene in T7SS functionality.IMPORTANCEPathogenic mycobacteria, such as the notorious Mycobacterium tuberculosis, are highly successful as pathogens, in part due to their specific and diderm cell envelope, with a mycolic acid-containing outer membrane. The architecture of this highly impermeable membrane is little understood and the proteins that populate it even less so. To transport proteins across their cell envelope, mycobacteria employ a specialized transport pathway called type VII secretion. While recent studies have elucidated the type VII secretion membrane channel that mediates transport across the inner membrane, the identity of the outer membrane channel remains a black box. Here, we show evidence that specific substrates of the type VII pathway could form these channels. Elucidating the pathway and mechanism of protein secretion through the mycobacterial outer membrane will allow its exploitation for the development of novel mycobacterial therapeutics.

In Situ Spectroscopic Detection of Large-Scale Reorientations of Transmembrane Helices During Influenza A M2 Channel Opening.

Viroporins are small ion channels in membranes of enveloped viruses that play key roles during viral life cycles. To use viroporins as drug targets against viral infection requires in-depth mechanistic understanding and, with that, methods that enable investigations under in situ conditions. Here, we apply surface-enhanced infrared absorption (SEIRA) spectroscopy to Influenza A M2 reconstituted within a solid-supported membrane, to shed light on the mechanics of its viroporin function. M2 is a paradigm of pH-activated proton channels and controls the proton flux into the viral interior during viral infection. We use SEIRA to track the large-scale reorientation of M2's transmembrane α-helices in situ during pH-activated channel opening. We quantify this event as a helical tilt from 26° to 40° by correlating the experimental results with solid-state nuclear magnetic resonance-informed computational spectroscopy. This mechanical motion is impeded upon addition of the inhibitor rimantadine, giving a direct spectroscopic marker to test antiviral activity. The presented approach provides a spectroscopic tool to quantify large-scale structural changes and to track the function and inhibition of the growing number of viroporins from pathogenic viruses in future studies.

In situ‐spektroskopische Detektion der weitreichenden Reorientierung von Transmembranhelices während der Öffnung des Influenza A M2‐Kanals**

AbstractViroporine sind kleine Ionenkanäle in Membranen umhüllter Viren, die Schlüsselrollen in viralen Lebenszyklen spielen. Um Viroporine als Wirkstoffziele zur Bekämpfung von Virusinfektionen nutzen zu können, bedarf es eines umfassenden Verständnisses ihrer Funktionsweise. Hierfür sind wiederum Methoden notwendig, die ihre Untersuchung unter in situ‐Bedingungen ermöglichen. In dieser Arbeit nutzen wir die oberflächenverstärkte Infrarotabsorptionsspektroskopie (SEIRA, engl. surface‐enhanced infrared absorption), um den Mechanismus der Viroporinfunktion von Influenza A M2 in einer trägergestützten Membran zu untersuchen. M2 ist ein Paradebeispiel pH‐aktivierter Protonenkanäle, das den Protonenfluss in das Virusinnere während einer Virusinfektion kontrolliert. Mit Hilfe von SEIRA verfolgen wir die weitreichende Reorientierung der transmembranen α‐Helices von M2 in situ während der pH‐aktivierten Kanalöffnung. Wir quantifizieren dieses Ereignis als eine helikale Neigung von 26° zu 40° durch eine Korrelation der experimentellen Ergebnisse mit rechnergestützter Spektroskopie basierend auf Strukturen aus Festkörper‐Kernspinresonanzspektroskopie. Die mechanische Bewegung wird durch die Zugabe des Inhibitors Rimantadin verhindert, was somit einen direkten spektroskopischen Marker zum Testen der antiviralen Aktivität darstellt. Der hier vorgestellte Ansatz bietet somit ein spektroskopisches Werkzeug zur Quantifizierung großskaliger Strukturänderungen und zum Beobachten der Funktion und Inhibition einer wachsenden Zahl von Viroporinen aus pathogenen Viren.

AAV-compatible optogenetic tools for activating endogenous calcium channels in vivo

Calcium ions (Ca2+) play pivotal roles in regulating diverse brain functions, including cognition, emotion, locomotion, and learning and memory. These functions are intricately regulated by a variety of Ca2+-dependent cellular processes, encompassing synaptic plasticity, neuro/gliotransmitter release, and gene expression. In our previous work, we developed ‘monster OptoSTIM1’ (monSTIM1), an improved OptoSTIM1 that selectively activates Ca2+-release–activated Ca2+ (CRAC) channels in the plasma membrane through blue light, allowing precise control over intracellular Ca2+ signaling and specific brain functions. However, the large size of the coding sequence of monSTIM1 poses a limitation for its widespread use, as it exceeds the packaging capacity of adeno-associated virus (AAV). To address this constraint, we have introduced monSTIM1 variants with reduced coding sequence sizes and established AAV-based systems for expressing them in neurons and glial cells in the mouse brain. Upon expression by AAVs, these monSTIM1 variants significantly increased the expression levels of cFos in neurons and astrocytes in the hippocampal CA1 region following non-invasive light illumination. The use of monSTIM1 variants offers a promising avenue for investigating the spatiotemporal roles of Ca2+-mediated cellular activities in various brain functions. Furthermore, this toolkit holds potential as a therapeutic strategy for addressing brain disorders associated with aberrant Ca2+ signaling.

Robust and highly reactive membranes for continuous disposal of chemical warfare agents: Effects of nanostructure and functionality in MOF and nanochitin aerogel composites

Developing appropriate disposal of stockpiles of chemical warfare agents (CWAs) has gained significant attention as their lethal toxicity seriously harms humanity. In this study, a novel green-fabrication method with UiO-66 catalysts and amine-functionalized chitin nanofibers (ChNFs) was suggested to prepare durable and highly reactive membranes for decomposing chemical warfare agents (CWAs) in the continuous flow system. The strong interaction between ChNFs and the UiO-66 led to stable loading of the UiO-66 on the continuous nano-porous channel of the ChNF reactive membrane even with high loading of UiO-66 (70 wt% of UiO-66 in the ChNF substrate). In addition, the Brønsted base functionalities (–NH2 and –NHCOCH3) of the ChNF enhanced the catalytic activity and recyclability of the UiO-66. The resulting 70-ChNF composites can effectively decompose a nerve agent simulant (methyl paraoxon) even after 7 repeatable cycles, which has been not obtained in the previous UiO-66 catalyst. The ChNF/UiO-66 reactive membranes with 1 m2 of the area decomposed 130 g of CWAs within an hour in a continuous flow system. We believe these robust and highly reactive membranes can provide a sustainable and efficient solution for the massive CWA disposal and also contribute to the advancement of functional membrane material science.